Gene expression and regulation in the extended longevity phenotypes of Drosophila.

We used both selection and single-gene mutagenesis studies to identify the mechanisms underlying the genetic control of longevity in Drosophila. The expression of the extended longevity phenotype (ELP) in our forward-selected strains depends on an early and specific upregulation of the antioxidant defense system (ADS) genes and enzymes, which results in decreased oxidative damage levels and a delayed onset of senescence. This mechanism does not alter metabolic rate and is itself reversed by a reverse selection regime. Single-gene mutational analysis of the regulatory genes controlling ADS gene expression show they are under the positive and negative control of several such genes, each of which can bring about the expression/repression of the ELP. Sister strains with identical ELPs have different patterns of ADS gene expression, showing that phenotypic equivalence does not require molecular equivalence. The organism may have multiple genetic strategies to cope with similar levels of oxidative stress.